Helen L Fisher1, Sarah Cohen-Woods2, Georgina M Hosang2, Rudolf Uher2, Georgia Powell-Smith2, Robert Keers2, Maria Tropeano2, Ania Korszun3, Lisa Jones4, Ian Jones5, Mike Owen5, Nick Craddock5, Ian W Craig2, Anne E Farmer2, Peter McGuffin2. 1. MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK. Electronic address: helen.2.fisher@kcl.ac.uk. 2. MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK. 3. Barts and The London School of Medicine and Dentistry, Queen Mary University of London - Centre for Psychiatry, London, UK. 4. Department of Psychiatry, School of Clinical & Experimental Medicine, University of Birmingham, Birmingham, UK. 5. Department of Psychological Medicine & Neurology, Cardiff University School of Medicine, Cardiff, UK.
Abstract
BACKGROUND: An interaction between recent stressful life events (SLEs) and a serotonin transporter promoter polymorphism (5-HTTLPR) in depression has been inconsistently reported. Some of this variability may be due to a previous focus on sub-clinical depression, inclusion of individuals at the lower or upper ends of the age-span, or assumptions concerning the degree of dominance of the low expressing allele. Therefore, a large sample of patients with recurrent clinically diagnosed depression and controls screened for absence of depression was utilised to examine the moderating effect of each 5-HTTLPR genetic model on the association between SLEs and severe depressive episodes. METHOD: A sample of 1236 recurrent unipolar depression cases and 598 age-matched, never psychiatrically ill controls completed the List of Threatening Experiences Questionnaire to assess the number of SLEs experienced in the 6 months prior to the most severe depressive episode (cases) or interview (controls). DNA extracted from blood or cheek swabs was genotyped for the short (s) and long (l) alleles of 5-HTTLPR. RESULTS: A greater number of SLEs were reported by cases than controls and this held across all genotypic groups. There was no main effect of 5-HTTLPR on depression and no evidence of interaction between total SLEs and any of the 5-HTTLPR genetic models. The results were the same for men and women. LIMITATIONS: Utilisation of retrospective self-reported SLEs may have reduced the accuracy of the findings and the cross-sectional design prevents causal inference. CONCLUSIONS: This study failed to find evidence of gene-environment interplay in recurrent clinical depression.
BACKGROUND: An interaction between recent stressful life events (SLEs) and a serotonin transporter promoter polymorphism (5-HTTLPR) in depression has been inconsistently reported. Some of this variability may be due to a previous focus on sub-clinical depression, inclusion of individuals at the lower or upper ends of the age-span, or assumptions concerning the degree of dominance of the low expressing allele. Therefore, a large sample of patients with recurrent clinically diagnosed depression and controls screened for absence of depression was utilised to examine the moderating effect of each 5-HTTLPR genetic model on the association between SLEs and severe depressive episodes. METHOD: A sample of 1236 recurrent unipolar depression cases and 598 age-matched, never psychiatrically ill controls completed the List of Threatening Experiences Questionnaire to assess the number of SLEs experienced in the 6 months prior to the most severe depressive episode (cases) or interview (controls). DNA extracted from blood or cheek swabs was genotyped for the short (s) and long (l) alleles of 5-HTTLPR. RESULTS: A greater number of SLEs were reported by cases than controls and this held across all genotypic groups. There was no main effect of 5-HTTLPR on depression and no evidence of interaction between total SLEs and any of the 5-HTTLPR genetic models. The results were the same for men and women. LIMITATIONS: Utilisation of retrospective self-reported SLEs may have reduced the accuracy of the findings and the cross-sectional design prevents causal inference. CONCLUSIONS: This study failed to find evidence of gene-environment interplay in recurrent clinical depression.
Authors: G M Hosang; A Korszun; L Jones; I Jones; J M Gray; C M Gunasinghe; P McGuffin; A E Farmer Journal: Psychol Med Date: 2010-02-05 Impact factor: 7.723
Authors: Helen L Fisher; Thomas K Craig; Paul Fearon; Kevin Morgan; Paola Dazzan; Julia Lappin; Gerard Hutchinson; Gillian A Doody; Peter B Jones; Peter McGuffin; Robin M Murray; Julian Leff; Craig Morgan Journal: Schizophr Bull Date: 2009-09-23 Impact factor: 9.306
Authors: Sarah Cohen-Woods; Daria Gaysina; Nick Craddock; Anne Farmer; Joanna Gray; Cerisse Gunasinghe; Farzana Hoda; Lisa Jones; Jo Knight; Ania Korszun; Michael J Owen; Abram Sterne; Ian W Craig; Peter McGuffin Journal: Hum Mol Genet Date: 2009-01-30 Impact factor: 6.150
Authors: Darya Gaysina; Sarah Cohen-Woods; Philip C Chow; Livia Martucci; Alexandra Schosser; Harriet A Ball; Federica Tozzi; Julia Perry; Pierandrea Muglia; Ian W Craig; Peter McGuffin; Anne Farmer Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2009-09-05 Impact factor: 3.568
Authors: Helen L Fisher; Sarah Cohen-Woods; Georgina M Hosang; Ania Korszun; Mike Owen; Nick Craddock; Ian W Craig; Anne E Farmer; Peter McGuffin; Rudolf Uher Journal: J Affect Disord Date: 2012-07-25 Impact factor: 4.839
Authors: Ruth Spence; Amanda Bunn; Stephen Nunn; Georgina M Hosang; Lisa Kagan; Helen L Fisher; Matthew Taylor; Antonia Bifulco Journal: JMIR Res Protoc Date: 2015-07-14
Authors: Matthew Owens; Ian M Goodyer; Paul Wilkinson; Anupam Bhardwaj; Rosemary Abbott; Tim Croudace; Valerie Dunn; Peter B Jones; Nicholas D Walsh; Maria Ban; Barbara J Sahakian Journal: PLoS One Date: 2012-11-28 Impact factor: 3.240
Authors: N Mullins; R A Power; H L Fisher; K B Hanscombe; J Euesden; R Iniesta; D F Levinson; M M Weissman; J B Potash; J Shi; R Uher; S Cohen-Woods; M Rivera; L Jones; I Jones; N Craddock; M J Owen; A Korszun; I W Craig; A E Farmer; P McGuffin; G Breen; C M Lewis Journal: Psychol Med Date: 2015-11-03 Impact factor: 7.723